Impact of Recurrent Epidemics of Hepatitis A Virus Infection on Population Immunity Levels: Bristol Bay, Alaska

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1 1081 Impact of Recurrent Epidemics of Hepatitis A Virus Infection on Population Immunity Levels: Bristol Bay, Alaska Dolly Peach, 1,a Brian J. McMahon, 1,2 Lisa Bulkow, 1 Elizabeth Funk, 3 Rafael Harpaz, 4 and Harold S. Margolis 5 1 Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 2 Viral Hepatitis Program, Alaska Native Medical Center, and 3 State of Alaska Department of Health and Social Services, Anchorage; 4 Epidemiology and Surveillance Branch, National Immunization Program, and 5 Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia The dynamics of population-based immunity were examined by using serologic surveys of 7 villages in rural Alaska between 2 epidemics of hepatitis A virus (HAV) and after the second epidemic ( ). Among persons aged 2 30 years, the overall age-adjusted prevalence of antibody to HAV (anti-hav) was 51% in 1983 and 49% in 1993 ( P p.506). In children aged!5 years, prevalence rates were 0% and 11% in 1983 and 1993, respectively. The prevalence of HAV infection increased with age in both surveys. When examined by 5-year birth cohorts, anti-hav prevalence increased in children born between 1979 and 1983 ( P!.001). Between the 2 survey periods, 43 clinical cases of HAV infection were reported in these villages; all occurred from 1988 to Despite high overall prevalence of immunity, transmission during epidemics was facilitated by children aged!15 years susceptible to HAV. Little transmission occurred between epidemics. Vaccination of children against HAV should prevent future epidemics. Limited population-based data are available to examine the relationship between the prevalence of immunity to hepatitis A virus (HAV) infection and the occurrence of community-wide epidemics of hepatitis A [1]. Recurrent HAV epidemics have been documented in Alaska [2]. These epidemics commonly affect most rural communities and last 1 year. From 1986 to 1992, there was a hepatitis A epidemic in Alaska, which spread to the Bristol Bay region in southwest Alaska during In this study, we evaluated data from serologic surveys conducted in the Bristol Bay region before and after the epi- Received 20 March 2002; revised 21 June 2002; electronically published 20 September Presented in part: Western Student Medical Research Forum, Carmel, California, 9 12 February All study participants or their parents or guardians gave written informed consent. Children aged 17 years were included only if they verbally agreed to participate. The Alaska Native Medical Center (ANMC) and Centers for Disease Control and Prevention (CDC) institutional review boards and the Bristol Bay Native Health Corporation (BBAHC) approved the study. US Department of Health and Human Services, BBAHC, and ANMC human experimentation guidelines were followed. The chairman of the Alaska Area Native Health Service institutional review board approved the anonymous survey of serum samples. Financial support: CDC. a Present affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. Reprints or correspondence: Dr. Brian J. McMahon, Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Dr., Anchorage, AK (bdm9@cdc.gov). The Journal of Infectious Diseases 2002;186: by the Infectious Diseases Society of America. All rights reserved /2002/ $15.00 demic to develop an understanding of the interaction between prior or herd immunity and epidemic HAV infection in isolated communities. Subjects and Methods Study populations. Between 1983 and 1987, 52,000 Alaska Natives were tested for markers of hepatitis B virus (HBV) infection as part of a comprehensive hepatitis B immunization program [3]. Serum samples obtained from this program were stored at 34.4 C. Subsequently, anonymous random population samples of serum specimens stratified by community of residence and year of birth were tested for anti-hav [4]. The randomization process (described in more detail in [4]) included a sample of 4 birth cohorts with a minimum of 20 persons per village [4]. More than 95% of the blood samples were collected between October 1983 and November From December 1993 through January 1994, a study to determine the prevalence of HBV infection among Alaska Natives in the Bristol Bay region of southwest Alaska was conducted in 7 villages [5]. All residents aged 2 30 years were invited to participate. Serum specimens from participants were tested for total antibody to HAV (anti-hav). The 7 study villages were selected because their population was 90% Yupik Eskimo, and these demographics had not changed over the years. About 30% of the population in the Bristol Bay region and 2% of the Alaska Native population of the state resided in these 7 villages at the time of the 2 surveys. We compared the prevalence of hepatitis A in 6 of the 7 villages for 2 time periods. One village was only tested in Laboratory studies. Serum samples from both the and 1993 study periods were tested for total anti-hav by use of a commercial competitive inhibition EIA (HAVAB; Abbott Lab-

2 1082 Peach et al. JID 2002;186 (15 October) Figure 1. Cases of hepatitis A in Alaska (all Alaska) and in 7 Bristol Bay villages (Bristol Bay), oratories). A positive test result was considered to be evidence of past HAV infection. Surveillance data Records of cases of clinical hepatitis from the 7 study villages reported to the Alaska Department of Health and Social Services from 1972 to 2000 were examined to determine whether they met the hepatitis A case definition. A case of acute hepatitis A was defined as a person with either clinical symptoms compatible with hepatitis (jaundice and elevated serum aminotransferase levels) who was either a contact of someone with laboratory confirmed acute hepatitis A or had a serum specimen positive for anti-hav IgM [6]. Statistical methods. The prevalence of anti-hav was examined in 5-year age-specific groups at the 2 cross-sectional study points. We used the Mantel-Haenszel, x 2, and Fisher s exact tests to compare the proportions of persons positive for anti-hav for each group. All P values were 2-tailed, and P!.05 was considered to be significant. Population prevalence rates and estimates of reported rates of hepatitis A were determined by using US census data on Alaska Natives. To compare rates for anti-hav across the 2 time periods and to account for the different age distributions of the samples, direct age-adjustment was done to the 1990 Alaska Native population. Results Hepatitis A incidence. Two epidemics of hepatitis A occurred in Alaska between 1974 and 2000, each lasting 6 9 years, with a 7-year period between the epidemics (figure 1). Between 1974 and 2000, 100 cases of hepatitis A were reported to the Alaska Department of Health and Social Services from the 7 Bristol Bay study villages; all cases occurred during times of the statewide epidemics, and no cases were reported between or after these epidemics. In all, 57 cases were reported during and 43 during (figure 1). During the latter epidemic, the estimated clinical attack rate for the entire population of these villages was 2.3% (43/1847). The attack

3 JID 2002;186 (15 October) Hepatitis A Immunity and Alaska Epidemics 1083 Table 1. Age-specific prevalence of hepatitis A virus infection, Bristol Bay Villages, Alaska, 1983 and Age group, years No. positive/no. tested (% [age adjusted]) P (age adjusted) 0 4!4 0/6 2/47 (4) 4 0/2 8/46 (17) Subtotal 0/8 10/93 (11) /18 (39) 90/153 (59) /15 (60) 75/129 (58) /11 (64) 42/74 (57) /25 (92) 32/56 (57) /8 (88) 70/99 (70).438 Total 53/85 (62 [51]) 319/604 (53 [49]).125 (.506) rate declined by age group: 4.4% (29/654) for children aged!15 years, 1.2% (6/510) for persons aged years, and!1% (3 persons) for village residents aged 130 years. Prevalence of anti-hav. In 1983, 950 Alaska Natives aged 2 30 years resided in the 7 study villages (1980 census). Of 85 serum specimens from persons in this age group randomly selected for testing from 6 of these villages, 53 (62%) were anti- HAV positive (table 1). Residents of 1 village (population!50 in 1983) were not tested. In 1993, an estimated 1847 Alaska Natives resided in the 7 study villages, including 1164 aged 2 30 years [7]. Of the latter, 604 (52%) participated in the study, 52.3% of whom were anti- HAV positive ( P p.125; 1983 vs prevalence). Among persons aged 2 30 years, the overall age-adjusted rate was 51% in 1983 and 49% in Children aged!4 years, who were born after the epidemic, had a seroprevalence of anti-hav of 4% (95% confidence interval, 0.5% 14.5%). In both study periods, anti-hav prevalence increased significantly with age, increasing to 70% among persons aged years ( P!.03; table 1). There was no significant difference in anti- HAV prevalence by sex at either time. When data were analyzed by 5-year birth cohorts, the prevalence of HAV infection among participants born between 1979 and 1983 increased from 0% in 1983 to 58% in 1993 (P!.001), whereas the prevalence in the cohort born between 1974 and 1978 increased from 44% to 58% ( P p.412; figure 2). Between the 2 survey periods, no change in the prevalence of infection was found among other 5-year birth cohorts, which suggests that few persons born before 1974 were affected by the epidemic. Overall, 40% of study participants born after 1968 (i.e., aged!15 years in 1983) were anti-hav positive in Ten years later, the prevalence of HAV infection in this birth cohort increased to 58% ( P!.001), an 18% increase. Most of this increase can be attributed to infections in the birth cohort, who would have been aged 5 11 years during the epidemic. In 1983, no significant differences in anti-hav prevalence (range, 46% 86%) were observed between villages ( P p.281; table 2). However, in 1993, the prevalence of previous HAV infection ranged from 3% to 83% among villages ( P!.001). During the epidemic, no cases of clinical hepatitis were reported from 2 villages (villages B and F). In one of these villages, none of the children born immediately before or during the epidemic (i.e., aged!10 years) was anti-hav positive in 1993 (table 2; village B). In addition, this village was the only one in which a decrease in anti-hav prevalence was observed, Figure 2. Prevalence of hepatitis A in 2 Alaska birth cohorts, 1983 and 1993

4 1084 Peach et al. JID 2002;186 (15 October) Table 2. Prevalence of hepatitis A virus (HAV) infection and reported cases of hepatitis A, Bristol Bay villages, Alaska, Village 1990 Population Anti-HAV, age 29 years P Anti-HAV, 1993, age!10 years Reported cases of hepatitis A, A 94 ND 9/73 (12) ND 3/33 (9) 3 B 152 6/13 (46) 1/40 (3)!.001 0/11 0 C 160 9/15 (60) 36/68 (53) /34 (41) 5 D /14 (86) 46/75 (61) /32 (44) 7 E /17 (59) 63/110 (57) /40 (30) 11 F 391 7/14 (50) 28/74 (38) /33 (30 ) 0 G 613 9/12 (75) 136/164 (83) /63 (75) 17 NOTE. not done. Unless otherwise noted, data are no. positive/no. tested (%). ND, and it appears to have been skipped by the epidemic. No clinical cases of hepatitis A were reported during the epidemic in a second village. However, there was a 30% prevalence of anti- HAV among children aged!10 years, and no overall change in prevalence of infection during the 2 sampling periods occurred (table 2; village F). In 4 of the other 5 villages, the prevalence of infection was 30% in children aged!10 years and 3 patients with hepatitis A were reported to the Alaska Department of Health and Social Services. Discussion A high prevalence rate of HAV infection and recurrent epidemics of hepatitis A due to person-to-person transmission occur in Alaska Native and American Indian populations [1 3, 8], populations classified as having a high endemicity of HAV infection [9]. The results of the present study indicate significant differences in the epidemiology of HAV infection between Alaska Native and American Indian populations. In Alaska Natives, HAV transmission was rare between epidemics, as shown by the very low anti-hav prevalence in children aged!4 years (born during the interepidemic period). This contrasts with findings in American Indian populations, such as the Sioux in South Dakota, where young children born before the onset of an epidemic had an anti-hav prevalence of 40% [1]. These findings indicate that, in some American Indian populations, ongoing endemic asymptomatic HAV transmission occurs among young children [1, 8]. The high endemicity of HAV infection found in American Indian/Alaskan Native populations is similar to that observed in many regions of the world where HAV is highly endemic and where most infections (usually asymptomatic) occur among very young children [10 14]. The pattern of HAV infection observed in the Bristol Bay region, one of little or no transmission between epidemics of hepatitis A, appears to have occurred in other isolated Alaskan Native communities. This pattern may result from the isolation of rural Alaskan villages. Unlike other Native American communities, these villages are often not connected by road and are accessible only by air or boat in the summer and by dog team or snow mobile in the winter, limiting the opportunity for introduction of HAV during interepidemic periods. A similar pattern was described in isolated South Pacific island populations [15], where HAV is introduced into highly susceptible childhood populations and conditions exist for efficient virus transmission, resulting in epidemics and a high prevalence of infection. Because endemic HAV transmission apparently did not occur between epidemics in Bristol Bay or other parts of Alaska, before an epidemic can occur HAV must be introduced into these communities when there is a large proportion of seronegative children aged!15 years. The relative isolation of these villages also might explain why some villages can be spared during HAV epidemics [4]. Large epidemics also occur in developing countries with transitional economies [16]. Seroprevalence and incidence data from our study indicate that the highest rates of HAV infection, both inapparent and symptomatic, occurred among persons aged!15 years. In the Bristol Bay area and in the Sioux Indian Nation [1], the overall prevalence of HAV infection in this age group was well under 50% before epidemics; during the epidemic period a substantial number of children in this age group became infected with HAV. After the majority of the population became immune through infection, person-to-person transmission could no longer be sustained and the epidemic ceased. When the epidemic in the Bristol Bay area extended to the northwestern Bering Sea and Arctic coastal communities in 1992 and 1993, a campaign was initiated to administer 1 dose of hepatitis A vaccine to uninfected children and young adults. When 79% of the susceptible persons of 11 isolated communities were immunized, cases of acute hepatitis A ceased within 8 weeks in each community. In contrast, when only 49% of susceptible persons were immunized in an adjacent large isolated community with persons, the epidemic continued for another 12 months. [17]. Similar experience with the use of hepatitis A vaccination to interrupt community-wide epidemics in New York state, Tennessee, and California suggests that immunization coverage rates of 60% 70% would interrupt HAV transmission [18 20]. These studies suggest that immunization efforts targeted at children aged!15 years that achieve 160% prevalence of anti-hav should interrupt HAV transmission in susceptible persons during an epidemic. In addition, maintaining high immunization coverage of children aged!15 years should prevent high endemic transmission of HAV infection, as well as future epidemics in communities with previous high rates of infection [6]. Routine hepatitis A vaccination of children aged 2 18 years was begun in Alaska in 1996 and should prevent future epidemics of hepatitis A. References 1. Shaw FE, Shapiro CN, Welty TK. Hepatitis transmission among the Sioux Indians of South Dakota. Am J Public Health 1990;80: Middaugh J. State of Alaska: infectious disease data. Alaska Department of Health and Social Services, Division of Public Health, 1987:

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